PUBLICATION

Neuron-Radial Glial Cell Communication via BMP/Id1 Signaling Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon

Authors
Zhang, G., Lübke, L., Chen, F., Beil, T., Takamiya, M., Diotel, N., Strähle, U., Rastegar, S.
ID
ZDB-PUB-211025-55
Date
2021
Source
Cells   10(10): (Journal)
Registered Authors
Beil, Tanja, Chen, Fushun, Lübke, Luisa, Rastegar, Sepand, Strähle, Uwe, Takamiya, Masanari, Zhang, Gaoqun
Keywords
BMP, adult neurogenesis, her4.1, id1, neural stem cell, notch, quiescence, radial glial cell, regeneration, telencephalon, zebrafish
MeSH Terms
  • Aging/physiology*
  • Animals
  • Bone Morphogenetic Proteins/metabolism*
  • Cell Communication*
  • Cell Cycle/genetics
  • Cell Proliferation
  • Ependymoglial Cells/cytology*
  • Gene Expression Regulation, Developmental
  • Neural Stem Cells/cytology
  • Neurons/cytology*
  • Receptors, Notch/metabolism
  • Regeneration/physiology*
  • Signal Transduction
  • Telencephalon/injuries
  • Telencephalon/pathology
  • Telencephalon/physiopathology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(all 19)
PubMed
34685774 Full text @ Cells
Abstract
The central nervous system of adult zebrafish displays an extraordinary neurogenic and regenerative capacity. In the zebrafish adult brain, this regenerative capacity relies on neural stem cells (NSCs) and the careful management of the NSC pool. However, the mechanisms controlling NSC pool maintenance are not yet fully understood. Recently, Bone Morphogenetic Proteins (BMPs) and their downstream effector Id1 (Inhibitor of differentiation 1) were suggested to act as key players in NSC maintenance under constitutive and regenerative conditions. Here, we further investigated the role of BMP/Id1 signaling in these processes, using different genetic and pharmacological approaches. Our data show that BMPs are mainly expressed by neurons in the adult telencephalon, while id1 is expressed in NSCs, suggesting a neuron-NSC communication via the BMP/Id1 signaling axis. Furthermore, manipulation of BMP signaling by conditionally inducing or repressing BMP signaling via heat-shock, lead to an increase or a decrease of id1 expression in the NSCs, respectively. Induction of id1 was followed by an increase in the number of quiescent NSCs, while knocking down id1 expression caused an increase in NSC proliferation. In agreement, genetic ablation of id1 function lead to increased proliferation of NSCs, followed by depletion of the stem cell pool with concomitant failure to heal injuries in repeatedly injured mutant telencephala. Moreover, pharmacological inhibition of BMP and Notch signaling suggests that the two signaling systems cooperate and converge onto the transcriptional regulator her4.1. Interestingly, brain injury lead to a depletion of NSCs in animals lacking BMP/Id1 signaling despite an intact Notch pathway. Taken together, our data demonstrate how neurons feedback on NSC proliferation and that BMP1/Id1 signaling acts as a safeguard of the NSC pool under regenerative conditions.
Genes / Markers
Marker Marker Type Name
ascl1aGENEachaete-scute family bHLH transcription factor 1a
bambiaGENEBMP and activin membrane-bound inhibitor (Xenopus laevis) homolog a
bmp2aGENEbone morphogenetic protein 2a
bmp2bGENEbone morphogenetic protein 2b
bmp4GENEbone morphogenetic protein 4
bmp7aGENEbone morphogenetic protein 7a
bmp7bGENEbone morphogenetic protein 7b
bmpr2bGENEbone morphogenetic protein receptor, type II b (serine/threonine kinase)
her4.1GENEhairy-related 4, tandem duplicate 1
id1GENEinhibitor of DNA binding 1, HLH protein
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Figures
Figure Gallery (7 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fr13TgTransgenic Insertion
    ka706
      Small Deletion
      ka710TgTransgenic Insertion
        ka711TgTransgenic Insertion
          ups4TgTransgenic Insertion
            vu12TgTransgenic Insertion
              y83TgTransgenic Insertion
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                id1CRISPR1-id1CRISPR
                id1CRISPR2-id1CRISPR
                id1CRISPR3-id1CRISPR
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                Fish
                1 - 5 of 5
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                Antibodies
                Name Type Antigen Genes Isotypes Host Organism
                Ab1-glulmonoclonal
                  IgG2aMouse
                  Ab1-neurod1monoclonal
                    IgG2aMouse
                    Ab1-s100polyclonalRabbit
                    Ab2-pcnamonoclonalIgG2aMouse
                    Ab5-elavlpolyclonal
                      IgGRabbit
                      Ab13-smadmonoclonal
                        IgGRabbit
                        1 - 6 of 6
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                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        CFPEFGCFP
                        EGFPEFGEGFP
                        mCherryEFGmCherry
                        1 - 3 of 3
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                        Mapping
                        No data available